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Clinical Trial
. 2016 Jan 19;114(2):163-70.
doi: 10.1038/bjc.2015.419. Epub 2015 Dec 10.

Predictive role of hand-foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer

Christoph Zielinski  1   2 , Istvan Lang  3 , Semir Beslija  4 , Zsuzsanna Kahan  5 , Moshe J Inbar  6 , Salomon M Stemmer  7 , Rodica Anghel  8 , Damir Vrbanec  9 , Diethelm Messinger  10 , Thomas Brodowicz  1   2
Affiliations
Clinical Trial

Predictive role of hand-foot syndrome in patients receiving first-line capecitabine plus bevacizumab for HER2-negative metastatic breast cancer

Christoph Zielinski et al. Br J Cancer. .

Abstract

Background: Correlations between development of hand-foot syndrome (HFS) and efficacy in patients receiving capecitabine (CAP)-containing therapy are reported in the literature. We explored the relationship between HFS and efficacy in patients receiving CAP plus bevacizumab (BEV) in the TURANDOT randomised phase III trial.

Methods: Patients with HER2-negative locally recurrent/metastatic breast cancer (LR/mBC) who had received no prior chemotherapy for LR/mBC were randomised to BEV plus paclitaxel or BEV-CAP until disease progression or unacceptable toxicity. This analysis included patients randomised to BEV-CAP who received ⩾1 CAP dose. Potential associations between HFS and both overall survival (OS; primary end point) and progression-free survival (PFS; secondary end point) were explored using Cox proportional hazards analyses with HFS as a time-dependent covariate (to avoid overestimating the effect of HFS on efficacy). Landmark analyses were also performed.

Results: Among 277 patients treated with BEV-CAP, 154 (56%) developed HFS. In multivariate analyses, risk of progression or death was reduced by 44% after the occurrence of HFS; risk of death was reduced by 56%. The magnitude of effect on OS increased with increasing HFS grade. In patients developing HFS within the first 3 months, median PFS from the 3-month landmark was 10.0 months vs 6.2 months in patients without HFS. Two-year OS rates were 63% and 44%, respectively.

Conclusions: This exploratory analysis indicates that HFS occurrence is a strong predictor of prolonged PFS and OS in patients receiving BEV-CAP for LR/mBC. Early appearance of HFS may help motivate patients to continue therapy.

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Conflict of interest statement

CZ has received honoraria from and acted as a consultant for Roche; SB has received honoraria from and acted as a consultant for Roche, Pfizer, AbbVie, and Novartis; ZK has acted as a consultant for Roche; DV has received honoraria from Roche and Novartis and has acted as a consultant for Roche and Sanofi Aventis; DM is an employee of a contract research organisation that provides services to F. Hoffmann-La Roche; and TB has received honoraria from Amgen, Bayer, GSK, Eli Lilly, Merck, Novartis, PharmaMar, PrimeOncology, and Roche, and has acted as a consultant for Amgen, Bayer, Novartis, and PharmaMar. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient flow. HFS=hand-foot syndrome.
Figure 2
Figure 2
Efficacy according to the development of HFS in patients receiving bevacizumab plus capecitabine treatment. (A) PFS; (B) OS. CI=confidence interval; HFS=hand-foot syndrome; OS=overall survival; PFS= progression-free survival.
Figure 3
Figure 3
Landmark-analysis patients experiencing HFS within the first 3 months of bevacizumab plus capecitabine treatment compared with those who had not experienced HFS at this landmark. (A) PFS (n=215); (B) OS (n=264). CI=confidence interval; HFS=hand-foot syndrome; OS=overall survival; PFS=progression-free survival.
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